Many health conditions are characterized by inflammation, whether from microbial infection, sterile insult, or both. Inflammatory conditions, regardless of origin, share similar symptoms such as pain, heat, redness, fever, rash or joint swelling, and lesions, including wounds and ulcers to the skin, among others. While often difficult to discern underlying causes in a particular case, pain is often a key indicator of inflammation, because the swelling of the affected area/organ is pushing against sensitive nerve endings which then send pain and/or itch signals to the brain.
Conditions involving inflammation may be treated with, for example, topical or systemic antibiotics, antivirals, and/or anti-inflammatory agents depending on the suspected etiology. Such treatments are however limited by age restrictions, microbial resistance, drug toxicity, irritation, hypersensitivity and/or other side effects that may occur or develop especially with chronic use.
For example, in one model of inflammation, inflammation is initiated by either pathogen-associated molecular patterns (or PAMPs) or damage (or danger)-associated molecular patterns (DAMPs). PAMPs are molecules associated with pathogens that are recognized by cells of the innate immune system. These molecules are recognized by Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs), and activate innate immune responses to protect the host from infection. DAMPs are molecules that can initiate and perpetuate a noninfectious inflammatory response, and are often cytosolic or nuclear components that are released from the cell, for example upon cell necrosis. Innate immune responses activated by PAMPs and DAMPs include inflammatory responses or inflammatory processes/cascades such as the inflammasome, which further include itch and pain mediators and their respective receptors, prurireceptors and nociceptors in the skin nerve terminal. Certain mediators of the inflammatory cascade are the same, whether initiated by PAMPs or DAMPs, and can include, α-2 macroglobulins, TNF-α, IL-2, IL-6, Il-1β, IL-8, TSLP, IL-4, IL-13, IL-17, IL-18, IL-31, among others.
It is an object of the invention to provide a broadly effective and safe treatment for conditions characterized by inflammation, whether originating from microbial or sterile insult, and such conditions include acute and chronic inflammation, as well as delayed-type and immediate-type hypersensitivity. It is also an object of the invention to provide a broadly effective and safe treatment for the prevention of diseases and conditions associated with or caused by prolonged or untreated inflammation. It is an object of this invention to provide compositions and methods that are safe and effective for prolonged and/or prophylactic use, by patients of all ages including pediatric and geriatric patients, and/or immunocompromised patients, for the prevention and management of inflammation.